The majority of cancerous tumors in humans occur in the lung, liver and kidney, with the majority of the tumors being solid. Lung cancer, specifically non-small cell lung cancer is a leading cause of cancer death in North America (Jemal et al 2005, McLoud 2002). Liver cancer or hepatocellular carcinoma, is another leading cause of cancer death affecting 1 million people worldwide with 5 year survival as low as 10% (Chiba et al 2005). In addition, Renal Cell Carcinoma (RCC), the most common form of kidney cancer, accounts for 31,000 new cases of cancer diagnosed each year in the U.S. (Moore et al 2005). In fact, the incidence of renal tumors is increasing as improvements in diagnostic imaging have lead to the increasing discovery of small renal masses less than 3 cm in diameter.
The majority of lung and liver cancer patients are diagnosed at an advanced stage of the disease, often with large tumors exceeding 3 cm in diameter (McLoud 2002; Beaugrand et al 2005), which have either been shown to have a high incidence of local recurrence following standard radiotherapy techniques or 3D conformal radiotherapy (Lagerwaard et al 2002), or cannot be resected. The treatment of choice for RCC is partial or complete surgical removal of the kidney, however the rising incidence and increased detection of small renal masses have stimulated interest in developing less radical therapeutic alternatives (Varkarakis et al 2005, Rendon et al 2001).
In the treatment of solid tumors the two main issues to contend with are pain management, and inhibition of tumor growth. Current treatments of tumors tend to address one or the other issue. These treatments include surgery, chemotherapy, cryosurgery, ethanol injection, radiation therapy, and interstitial thermal therapy.
Surgery is considered to be the “gold standard” in the treatment of liver tumors. However, 70 to 90% of liver cancer patients are unresectable, meaning that they do not qualify for surgery because of limited liver function and/or unfavourable anatomy. Generally, about 15% of the patients with tumors less than 2 cm are amenable to resection. The few patients who do qualify for surgery have a 2% mortality rate and cannot be re-operated on in the likely occurrence of tumor regrowth. For lung cancer, surgery is the treatment of choice, with 5-year survival rates of 50-70% (Mountain 1997). However, only 20% of lung cancer patients are amenable to this procedure. Furthermore, in general, surgery typically limits organ function afterwards.
Chemotherapy has also been used locally and systemically for treatment of liver cancer tumors. However, there is an increase in pain for the patient as well as significant side effects such as vomiting, ulcerations and risk of infection. Chemotherapy inhibits tumor growth but generally is not an effective treatment because of excessive toxicity and lack of survival benefit.
In cryosurgery, steel probes are used to deliver liquid nitrogen to freeze the tumor. However, the freeze-thaw cycle of this procedure may cause organ damage or hemorrhaging to the organ that contains the tumor. For instance, with liver tumors, cryosurgery inhibits the tumor but weakens the liver. Furthermore, cryosurgery is not an option for non-resectable tumors, and multiple treatments are generally required.
Percutaneous ethanol injection involves injection of alcohol into the tumor. This procedure requires multiple treatments and may lead to pain. Furthermore, this procedure can weaken the organ that contains the tumor, is ineffective on large tumors and multiple treatments are usually required.
Radiation therapy is infrequently used in the treatment of liver cancer. It is not effective and can actually be more harmful to the patient, causing radiation hepatitis and death. Meanwhile, when radiation therapy is used with patients having lung tumors that are non-surgical candidates, 10-34% of these patients survive to 5 years depending on the stage of the disease (Kong et al 2005). For those patients with locally advanced unresectable disease treated with radiotherapy alone, 5-year survival is less than 10%, with 45% of patients having isolated local failure.
Interstitial thermal therapies have been developed to improve local tumor control in a minimally invasive manner using heat in the range of 50°-90° C. Interstitial applicators are delivered through laparoscopy or percutaneously, and localize thermal energy to the target volume. A variety of non-ionizing energy sources are currently used for interstitial thermal therapy including laser, microwave, ultrasound and radio frequency (RF) energy. Laser-induced interstitial thermotherapy uses light to thermally coagulate small (<2 cm), solid tumors. Microwave thermal therapy typically uses energy at frequencies of 433, 915 and 2450 MHz to heat and coagulate tissue. Interstitial ultrasound uses high intensity acoustic energy in the range of 2 MHz-10 MHz to thermally coagulate tissues.
RF thermal therapy, also known as RF ablation (RFA), is a relatively new treatment that is minimally invasive and so can be used on patients where open surgery is contraindicated. Moreover, unlike other treatments, RFA has thus far proven to be unhampered by many of the above-mentioned limitations of conventional treatments and repeat RFA treatments can be administered without toxicity. There is no known contra-indication for the use of RFA before or after treatments. RFA can also be used in conjunction with other therapies. Clinically, RFA has been approved or is under investigation for a range of malignancies in liver, bone, lung and kidney.
RFA conventionally uses RF energy in the range of 460-500 KHz to elevate temperatures sufficient to induce coagulative necrosis. Examples of RF applicators include monopolar needle electrodes and retractable curved electrodes having an umbrella shape, which require an external ground plane to complete the current path. In RFA therapy, the metal electrode is inserted into the tumor and is heated to 55-90° C. by a radio frequency driving current. Thermal conduction is then used to ‘spread’ the heat throughout the tumor. However, heat sinks, such as perfusion for example, limit the effectiveness of this heat transfer mechanism. For instance, renal ablation studies in porcine models by Rendon et al. (2001) indicated that lesion size was not reproducible due to renal blood flow, which limited therapeutic heating within the boundaries of the umbrella electrode that was used.
Furthermore, conventional RFA technology suffers from small, non-uniform, heating fields when using single interstitial therapy applicators. For instance, the needle electrodes produce small volumes of coagulated tissue, typically 1-2 cm in diameter, while the umbrella electrode produces at most, a 3 cm diameter ablation (McGahan and Dodd 2001). In the liver, Varkarakis (2005) showed that large (>3 cm) renal tumors were difficult to treat with conventional RF ablation and had a tendency for recurrence. In fact, McGahan and Dodd recommended that the largest tumor that should be treated by a single RF ablation electrode should be smaller than 2 cm in diameter. Larger tumors (>3 cm in diameter) require an array of applicators or multiple insertions of a single applicator in order to heat the whole tumor to cytotoxic levels, resulting in a more invasive procedure. Also, the ability to generate a uniform treatment field throughout a large target volume, necessary for local tumor control, is difficult when multiple applicators are used simultaneously, or when the tumor is highly vascular.